Q99741 (CDC6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cell division control protein 6 homolog

Alternative name(s):
CDC6-related protein
Cdc18-related protein
Short name=HsCdc18
p62(cdc6)
Short name=HsCDC6

Gene names

Name:	CDC6
Synonyms:	CDC18L

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	560 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.
Subunit structure	Interacts with PCNA, ORC1L, cyclin-CDK and HUWE1. Ref.2 Ref.5
Subcellular location	Nucleus. Cytoplasm. Note: The protein is nuclear in G1 and cytoplasmic in S-phase cells. Ref.2
Involvement in disease	Meier-Gorlin syndrome 5 (MGORS5) [MIM:613805]: A syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10
Sequence similarities	Belongs to the CDC6/cdc18 family.

Ontologies

Keywords
Biological process	Cell cycle Cell division DNA replication Mitosis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Dwarfism
Ligand	ATP-binding Nucleotide-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication Traceable author statement. Source: Reactome DNA replication checkpoint Traceable author statement Ref.2. Source: ProtInc M/G1 transition of mitotic cell cycle Traceable author statement. Source: Reactome S phase of mitotic cell cycle Traceable author statement. Source: Reactome cell division Inferred from electronic annotation. Source: UniProtKB-KW mitosis Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of DNA replication Traceable author statement Ref.2. Source: ProtInc negative regulation of cell proliferation Traceable author statement Ref.2. Source: ProtInc positive regulation of cell cycle cytokinesis Inferred from mutant phenotype PubMed 21041660. Source: BHF-UCL positive regulation of chromosome segregation Inferred from direct assay PubMed 21041660. Source: BHF-UCL regulation of cyclin-dependent protein serine/threonine kinase activity Traceable author statement Ref.2. Source: ProtInc regulation of mitotic anaphase Inferred from mutant phenotype PubMed 21041660. Source: BHF-UCL regulation of transcription involved in G1/S phase of mitotic cell cycle Traceable author statement. Source: Reactome traversing start control point of mitotic cell cycle Traceable author statement Ref.2. Source: ProtInc
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome spindle midzone Inferred from direct assay PubMed 21041660. Source: BHF-UCL spindle pole Inferred from direct assay PubMed 21041660. Source: BHF-UCL
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW chromatin binding Inferred from electronic annotation. Source: Compara nucleoside-triphosphatase activity Inferred from electronic annotation. Source: InterPro nucleotide binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDT1	Q9H211	3	EBI-374862,EBI-456953

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 560	560	Cell division control protein 6 homolog		PRO_0000150979
Regions
	Nucleotide binding	202 – 209	8	ATP Potential
Amino acid modifications
	Modified residue	45	1	Phosphoserine Ref.7
	Modified residue	54	1	Phosphoserine Ref.8
	Modified residue	127	1	Phosphoserine Ref.8
Natural variations
	Natural variant	238	1	T → A. Ref.3 Corresponds to variant rs4135010 [ dbSNP | Ensembl ].		VAR_019349
	Natural variant	295	1	D → N. Ref.3 Corresponds to variant rs4135012 [ dbSNP | Ensembl ].		VAR_019350
	Natural variant	299	1	T → M. Ref.3 Corresponds to variant rs4135013 [ dbSNP | Ensembl ].		VAR_019351
	Natural variant	323	1	T → R in MGORS5. Ref.10		VAR_065493
	Natural variant	378	1	R → H. Ref.3 Corresponds to variant rs4135016 [ dbSNP | Ensembl ].		VAR_019352
	Natural variant	441	1	V → I. Ref.3 Ref.4 Corresponds to variant rs13706 [ dbSNP | Ensembl ].		VAR_019353

Sequences

	Sequence		Length	Mass (Da)
	Q99741 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 3ED7DE4AF80CB017	FASTA	560	62,720
	10 20 30 40 50 60 MPQTRSQAQA TISFPKRKLS RALNKAKNSS DAKLEPTNVQ TVTCSPRVKA LPLSPRKRLG 70 80 90 100 110 120 DDNLCNTPHL PPCSPPKQGK KENGPPHSHT LKGRRLVFDN QLTIKSPSKR ELAKVHQNKI 130 140 150 160 170 180 LSSVRKSQEI TTNSEQRCPL KKESACVRLF KQEGTCYQQA KLVLNTAVPD RLPAREREMD 190 200 210 220 230 240 VIRNFLREHI CGKKAGSLYL SGAPGTGKTA CLSRILQDLK KELKGFKTIM LNCMSLRTAQ 250 260 270 280 290 300 AVFPAIAQEI CQEEVSRPAG KDMMRKLEKH MTAEKGPMIV LVLDEMDQLD SKGQDVLYTL 310 320 330 340 350 360 FEWPWLSNSH LVLIGIANTL DLTDRILPRL QAREKCKPQL LNFPPYTRNQ IVTILQDRLN 370 380 390 400 410 420 QVSRDQVLDN AAVQFCARKV SAVSGDVRKA LDVCRRAIEI VESDVKSQTI LKPLSECKSP 430 440 450 460 470 480 SEPLIPKRVG LIHISQVISE VDGNRMTLSQ EGAQDSFPLQ QKILVCSLML LIRQLKIKEV 490 500 510 520 530 540 TLGKLYEAYS KVCRKQQVAA VDQSECLSLS GLLEARGILG LKRNKETRLT KVFFKIEEKE 550 560 IEHALKDKAL IGNILATGLP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A human protein related to yeast Cdc6p." Williams R.S., Shohet R.V., Stillman B. Proc. Natl. Acad. Sci. U.S.A. 94:142-147(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase." Saha P., Chen J., Thome K.C., Lawlis S.J., Hou Z.H., Hendricks M., Parvin J.D., Dutta A. Mol. Cell. Biol. 18:2758-2767(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, INTERACTION WITH PCNA; ORC1 AND CYCLIN-CDK.
[3]	NIEHS SNPs program Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-238; ASN-295; MET-299; HIS-378 AND ILE-441.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-441. Tissue: Brain.
[5]	"Cdc6 stability is regulated by the Huwe1 ubiquitin ligase after DNA damage." Hall J.R., Kow E., Nevis K.R., Lu C.K., Luce K.S., Zhong Q., Cook J.G. Mol. Biol. Cell 18:3340-3350(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUWE1.
[6]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54 AND SER-127, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"Mutations in the pre-replication complex cause Meier-Gorlin syndrome." Bicknell L.S., Bongers E.M., Leitch A., Brown S., Schoots J., Harley M.E., Aftimos S., Al-Aama J.Y., Bober M., Brown P.A., van Bokhoven H., Dean J., Edrees A.Y., Feingold M., Fryer A., Hoefsloot L.H., Kau N., Knoers N.V. , Mackenzie J., Opitz J.M., Sarda P., Ross A., Temple I.K., Toutain A., Wise C.A., Wright M., Jackson A.P. Nat. Genet. 43:356-359(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MGORS5 ARG-323.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U77949 mRNA. Translation: AAB38317.1.
AF022109 mRNA. Translation: AAC52071.1.
AY150310 Genomic DNA. Translation: AAN10296.1.
BC025232 mRNA. Translation: AAH25232.1.

IPI

IPI00014575.

RefSeq

NP_001245.1. NM_001254.3.

UniGene

Hs.405958.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CCH	X-ray	1.70	E/F	89-100	[»]
2CCI	X-ray	2.70	F/I	74-100	[»]

ProteinModelPortal

Q99741.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-28154N.

IntAct

Q99741. 17 interactions.

MINT

MINT-1201847.

STRING

9606.ENSP00000209728.

PTM databases

PhosphoSite

Q99741.

Polymorphism databases

DMDM

50400620.

Proteomic databases

PaxDb

Q99741.

PRIDE

Q99741.

Protocols and materials databases

DNASU

990.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000209728; ENSP00000209728; ENSG00000094804.

GeneID

990.

KEGG

hsa:990.

UCSC

uc002huj.1. human.

Organism-specific databases

CTD

990.

GeneCards

GC17P038443.

HGNC

HGNC:1744. CDC6.

HPA

HPA050114.

MIM

602627. gene.
613805. phenotype.

neXtProt

NX_Q99741.

Orphanet

2554. Ear-patella-short stature syndrome.

PharmGKB

PA26271.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1474.

HOGENOM

HOG000045316.

HOVERGEN

HBG050860.

InParanoid

Q99741.

KO

K02213.

OMA

ATISFPK.

OrthoDB

EOG45756C.

PhylomeDB

Q99741.

Enzyme and pathway databases

Reactome

REACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.
REACT_383. DNA Replication.

Gene expression databases

Bgee

Q99741.

CleanEx

HS_CDC6.

Genevestigator

Q99741.

GermOnline

ENSG00000094804. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.10. 1 hit.

InterPro

IPR003593. AAA+_ATPase.
IPR015163. Cdc6_C_dom.
IPR016314. Cell_div_Cdc6/18.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]

Pfam

PF09079. Cdc6_C. 1 hit.
[Graphical view]

PIRSF

PIRSF001767. Cdc6. 1 hit.

SMART

SM00382. AAA. 1 hit.
SM01074. Cdc6_C. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q99741.

GenomeRNAi

990.

NextBio

4156.

PMAP-CutDB

Q99741.

SOURCE

Search...

Entry information

Entry name

CDC6_HUMAN

Accession

Primary (citable) accession number: Q99741
Secondary accession number(s): Q8TB30

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 114 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.